Cyclopropanecarboxylic acid esters



United States ABSTRACT OF THE DISCLOSURE A cyclopropanecarboxylic acid ester consisting of chrysanthemum monocarboxylic acid as the acid moiety and an N-hydroxymethyl succinimide derivative as the alcohol moiety was prepared. The ester possesses significant insecticidal power but is harmless to warm-blooded animals.

This invention relates to novel cyclopropanecarboxylic acid esters. More particularly, it relates to novel cyclopropanecarboxylic acid esters having the general formula:

wherein G is a member selected from the group consisting of groups, wherein R and R each mean a member selected from the group consisting of hydrogen atom, and methyl radical, and R and R each mean a member selected from th group consisting of hydrogen atom, and methyl and phenyl radicals; and R is a member selected from the group consisting of hydrogen atom, and methyl and ethyl radicals.

It is one object of the present invention to provide a novel group of cyclopropanecarboxylic acid esters, particularly of chrysanthemic acid esters, which have strong insecticidal activities to house and agricultural insects with low toxicities to warm-blooded animal and plants, and which can be commercially produced in low cost. Other objects will be obvious from the following description.

As an insecticide utilizable with safety because of the harmlessness to Warm-blooded animals, pyrethrum extract has long been employed. Recently, allethrin which is an analogue of the effective ingredients in pyrethrum extract, i.e. pyrethrin and cinerin, was synthesized and atent Ofifice 3,377,356 Patented Apr. 9, 1968 developed for insecticidal uses. These ingredients are certainly valuable in their high insecticidal powers, especially in their rapid effect on insects, and in the characteristics of permitting no, or little, resistivity to insects. However, their uses are limited to some extent because of their complicated steps of the production and their great expense for the production.

The present inventors have made broad researches on the various cyclopropanecarboxylic acid esters, and have now found the present novel group of cyclopropanecarboxylic acid esters, which possess significant insecticidal power but are harmless to warm-blooded animals, and which can be prepared from easily available materials by a simple process with low prices. In other words, the present compounds are succinimidomethyl and itaconimidomethyl esters of chrysanthemic acid. Accordingly, it is significant that the characteristics of the present compounds resemble py-rethrin, cinerin and allethrin, even though the alcohol moieties of the former are extremely simple as compared to those of the latter and are composed of carbon, hydrogen, oxygen, and nitrogen atoms, unlike the latter composed of carbon, hydrogen and oxygen.

Thus, the present invention is to provide novel cyclopropanecarboxylic acid esters having the formula,

wherein G and R have the same meanings as identified above, and to provide a process for preparing such compounds, comprising esterifying an imide compound having the general formula,

wherein G and R have the same meanings as identified above, with a cyclopopanecarboxylic acid having the formula,

/CH3 HOOCCE;CHCH=O CH3 CH3 CH3 according to the general esterifying procedure.

The imide compounds employed in the present invention, in other words, N-methylol-succinimides and N-methylol-itaconimides, or N (hydroxymethyl) -succinimides and N-(hydroxymethyl)-itaconimides, may be prepared from succinic acid, itaconic acid, their anhydrides, their imide compounds, or their substituted compounds, according to the procedures well-known to those skilled in the art. For instance, N-(hydroxymethyl)-succinimide may be prepared by reaction of succinimide with formaldehyde or its low molecular weight polymer according to the conventional methylolation conditions in the presence or absence of an alkaline catalyst, such as sodium hydroxide and potassium carbonate, in a solvent, such as water, benzene, and toluene. Similarly, various N-(hydroxymethyl) succinimide and N-(hydroxymethyl)-itaconimide, such as N (hydroxymethyl) succinimide, N (hydroxymethyl)-e-methylsuccinimide, N-(hydroxymethyl) cc ethyl succinimide, N (hydroxymethy1)-a,)8- dimethyl succinimide, N-(hydroxymethyl)-a,u-dimethylsuccinimide, N (hydroxymethyl)-u-methyl-fl-ethylsuccinimide, N (hydroxymethyl) itaconimide, N-(hydroxymethyl) v methylitaconimide, N-(hydroxymethyD-y-ydimethylitaconimide, N- (hydroxymethyl -phenylitaconimide, N- (hydroxymethyl -methyl-'y-phenylitaconimide, N (hydroxymethyl) 'y-y diphenylitaconimide, N-(hydroxymethyl)-a-methyl-y'y-dimethylitaconimide, N (hydroxymethyD-a-ethyl 'y'ydimethylitaconimide, and the like compounds may be prepared.

The cyclopropanecarboxylic acid employed in the present invention is chrysanthemic acid (chrysanthemum monocarboxylic acid). It is the acidic moieties of pyrethrin I, cinerin I and allethrin, and can be synthesized according to the known method.

The esterification reaction of the present invention may be effected in various Ways. The imide compound may be heated with the cyclopropanecarboxylic acid in the presence of a strong acid, such as aromatic sulfonic acid and sulfuric acid, in an organic solvent capable of azeotropically boiling with water, thereby removing from the reaction system the water formed in the esterification. It may also be heated with a lower alkyl ester of the cyclopropanecarboxylic acid in the presence of a basic catalyst, such as sodium, potassium, sodium alcoholate and potassium alcoholate, thereby to continuously remove the lower alcohol formed through the trans-esterification reaction out of the reaction system. In such a case, methyl, ethyl, n-propyl and isopropyl ester are suitable. In the most preferable esterification procedure, it may be treated with the cyclopropanecarboxylic acid halide in an inert organic solvent, preferably in the presence of a dehydrohalogenating agent, such as pyridine, triethylamine and other tertiary amine whereby the esterification proceeds with the isolation of a hydrohalic acid salt within a short period of time. In this case, the acid chloride is the most preferable, though the bromide and the iodide may be employed. Further, it may be refluxed with the cyclopropanecarboxylic acid anhydride in an inert solvent for several hours, thereby to yield the ester required and free cyclopropanecarboxylic acid, the latter being recovered and again converted to the anhydride by treatment with, for example, acetic anhydride for reuse. Alternatively, the imide compound may be employed for the esterification by once converted to the form of the halide having the general formula,

wherein G and R have the same meanings as identified above, and A means a halogen atom. In this case, the halide may be heated with an alkali metal or ammonium salt of the cyclopropanecarboxylic acid in an inert solvent, thereby to yield the ester required with the isolation of an alkali metal or ammonium halide salt. Alternatively, the halide may be heated with the free acid in an inert solvent in the presence of a dehydrohalogenating agent, such as tertiary amines. In the formula, A may be any of chlorine, bromine, and iodine, among which the former two are preferable and more practicable. As the alkali metals, sodium and potassium are preferable.

As is well-known, the cyclopropanecarboxylic acid as identified above comprises various stereoisomers and optical isomers. It is needless to say that the acid and the derivatives thereof as described herein involve their isomers.

The process of the invention is described in more detail with reference to the following examples, which are however to be construed for the purpose of illustration and not of limitation. All parts are by weight.

EXAMPLES Method A.A method which employs acid chloride Zero point one mol of an N-(hydroxymethyl)-succinimide or an N-(hydroxymethyl)-itaconimide was dissolved in a mixture of 0.15 mol of dry pyridine and 100 ml. of dry toluene. On the other hand, 0.102 mol of chrysanthemoyl chloride was dissolved in 50 ml. of dry toluene. When both solutions were mixed at a temperature of lower than 40 C., an exothermic reaction started, separating white crystals of pyridine hydrochloride. The reaction mixture was tightly closed with a stopper and allowed to stand overnight and then washed successively with 5 percent hydrochloric acid, saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution and dried over anhydrous magnesium sulfate. The solution was filtered and the filtrate was purified by passing through an alumina column, freed from toluene at a reduced pressure and further freed from remaining toluene at highly reduced pressure (0.01 mm. Hg), thereby colorless or pale yellowish viscous oily or crystalline ester was obtained.

Method B.-A method which uses acid anhydride Zero point one mol of an N-(hydroxymethyD-succinimide or. an N-(hydroxymethyl)-itaconimide was admixed with 0.1 mol of chrysanthemic acid anhydride and 100 ml. of dried toluene and stirred at a temperature of to C. for 3 hours. After cooling the mixture was treated with saturated sodium bicarbonate solution at a temperature lower than 10 C. to eliminate by-product, chrysanthemic acid and then washed with saturated aqueous solution of sodium chloride. The organic layer was dried over anhydrous magnesium sulfate and then treated in similar way as in the Method A to obtain ester.

Method C.-A method which uses acid Zero point one mol of an N-(chloromethyl)-succinimide or an N-(chloromethyl)-itaconimide obtained by the reaction of an N-(hydroxymethyl)-succinimlde or an N-(hydroxymethyl)-itaconimide with thionyl chloride or phosphorus trichloride at room temperature and 0.1 mol of chrysant-hemic acid were dissolved in 200 ml. of dried acetone. While agitating the mixture, 0.11 mol of triethylamine was dropped therein and the mixture was refluxed for 2 hours. After completion of the reaction, the mixture was cooled and separated from crystals of triethylarnine hydrochloride salt by filtration. Acetone was distilled off from the filtrate at a reduced pressure. The residue was dissolved in 100 ml. of toluene, washed successively with saturated aqueous solution of sodium bi carbonate and saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. The product of ester was obtained by the similar treatment as in the Method A thereafter.

The examples conducted in accordance with the abovementioned procedure are shown in the following Tables I and II.

TABLE ll continued Ester produced Example Esterifi- No. N-(hydroxymethyl) itaeonimide used cation Yield Elementary analysis (percent) method Formula Property (percent) C H N 12 H3O CO B cisHraNOrvfl MP. 8790 C 81 Found 67.88 7. 99 4, 2'2 Calcd 67. 71 7. s4 4. 39 I N-omou H30 H26 r 13 1130 CO C C II NOL Ml. 8890 G n. 85 Found. 67. 80 7. 97 4. 46 C-alcd 67. 71 7.34 4, 39

(3:0 I NCH1GH H 6 1120 (Used after chlorination) 14 C|1H5 CO A C$3H2QNO4, um; 1.5713 78 Found... 76. 31 6.96 2.79 Caled 75. as a. 55 a. to

(3:0 l N CH2OH CrHs H20 C 0 l5 r CO C C2zIlg5NOg l Mlr 153-155 C. 86 Found. 72. 09 7. 03 3. 91 Cfllcd 71. 93 6. 81 3. 81 C6H5CHZC I NC H1O H H (Used alter ehlon'natlou) 16 1 CsHs CO A CgaH;:NO4 11,1321 l.5385 8U FOIIIHLUH 72.91 7.35 3.25 Calcd 72. 44 7. 09 3. 67

0:0 H-CHlOH CH; H2O

17 H CO A CwHzrNO; .0 R1325 1.5115 e, 75 Found"... 68.34 8.64 3.88 Calcd 68. 41 8.11 4,20 I N-cmorr 1110 HC CH; C 0 l8 H30 CO A C20H2aN0 77,1327 1.5093 80 F01111(1 69.36 8. 51 3. 87 Caled 69,16 8. as 4.03 N-OHrOH HsC C\ H5 C: C 0

As mentioned above, the present esters possess superior insecticidal power, and exhibit rapid knock down and excellent killing effect on e.g. house flies, mosquitoes, cockroaches. Moreover, these esters are especially useful for sanitary and domestic purposes, because of their rapid effectiveness and harmlessness. The present esters are suitably employed for the preparation of insecticidal compositions which have broad uses, correlatively with the low cost.

For the formulation of the insecticidal composition containing the present compound as the essential ingredient, oil solution, emulsifiable concentrate, Wettable powder, dust, aerosol, mosquito coil (a burning incense device for warding ofi mosquitoes), bait and other preparation, may be formulated using generally employed carriers, diluents or auxiliary agents, according to the method known to those skilled in the art in the cases of the formulation of pyrethrum extract and allethrin. If the compound is crystalline, it is preferably employed as a preliminarily prepared solution in an organic solvent, such as acetone, xylene, methylnaphthalene, depending upon the type of the formulation.

If desired, the present esters may be employed for the preparation of the insecticidal compositions in combination with another insecticidal component, such as pyrethroide, for example, pyrethrum extract and allethrin, organochlorine and organophosphorus compounds, synergistic agent for pyrethroide, for example, piperonyl butoxide, piperonyl sulfoxide, fi-butoxy-H-thiocyanodiethyl ether and the like. By combination with such other ingredient, the present insecticidal composition can be adapted to broader uses with increased effect.

The present ester-s may be blended with at least one of pyrethrin, allethrin, 0,0-dimethyl-O-(3-mcthyl-4-nitrophenyl) thiophosphate, Malathiontrademark, diazinone, dimethoate, 'y-BHC, and others, to yield a pesticidal composition which possesses high insecticidal activity with rapid eifectivity. In such cases, the two components may be blended in a broad range of proportions, for example, in ratio of 0.05 :1 to 1:0,.05 by weight of the ester to another insecticidal component.

The present esters are comparatively stable. However, if the present esters are intended to be stored under a severe condition for along period of time, they may preferably be added with a small amount of a stabilizer, for Ltd.) were admixed in this order and dissolved with stirexample, alkylphenol compounds such as those having ring to obtain an emulsifiable concentrate.

the formula House flies (adult, a group of about 50 flies) were OH OH liberated in a high Petri dish and after covered with a l metal net lid, the Petri dish was charged to the bottom of 0mm)3 a settling-tower (McCallan, S. E. A., Contributions of containing Boyce Thompson, Inst. vol. 12, P-451, 1942). Ten mls.

G CH3)3 of the solution obtained by diluting the above-mentioned emulsifiable concentrate 20 times with water was sprayed upward at a pressure of 20 lbs. per sq. in. After 20 seconds, the shutter was opened, the house flies were exposed I to the descending mist for 10 minutes, taken out and placed in a room kept at a temperature of 27 C. The mortality was 85.3 percent after hours.

15 EXAMPLE 21 One point five grams of N-(chrysanthemoxymethyl)-u- CH3 ethylsuccinimide was dissolved in 30 mls. of acetone and OH OH admixed with 98.5 g. of mosquito coil carrier (a blend of tabu powder and pyrethrum marc in 2:3 proportion by weight) homogeneously with stirring. After evaporating (CHEW CH C(CHm acetone, 100 mls. of water was added to the above-mentioned mixture. Resulting mass was sufiiciently kneaded,

moulded into a coil and dried, whereby a mosquito coil CH3 CH3 25 containing 1.5 percent by weight of active ingredient was obtained.

03 I About northern house mosquitoes were liberated in I a glass box of 70 cm. cube and 1 g. piece of the above- CH2 H mentioned mosquito coil was hold horizontally on a go mosquito coil holder placed on the central part of the bottom of the box. Both ends of the coil were ignited and knock down number of northern housemosquitoes was CH1 CH3 observed relative to elapsed time. The result is shown as The amount of the stabilizer, if added, may be less than follows: 1% by weight of the present ester, ordinarily from 1 to s)aC (C rQs 0.1% Knock down ratio of northern house mosquitoes relative to elapse of time (percent) The following are examples of insecticidal compositlons I 7 containing the cyclopropanecarboxylic acid esters accord- 3 6 12 24 48 ing to the invention and of the insecticidal activities. Parts The Present 1.5% are y weight. 40 mosquito coil 9.0 22.0 42.6 59.4 81.3

EXAMPLE 19 Two parts of N-(chrysanthemoxymethyl)-succinimide- EXAMPLE 22 were dissolved in 15 parts of xylene and refined kerosene Zero point five part of N-(chrysanthemoxymethyD- was added to the resulting mixture to make the volume, u,fl-dimethylsuccinimide was dissolved in refined kerosene 100 ml., whereby 2 percent by weight of oil preparation so as to make the volume 100 mls., whereby 0.5 percent was obtained. by weight of oil preparation was obtained.

With use ofa Campbells Turn-table (Campbell, F. L., About 30 house flies (adult) were liberated in a 70 cm. Sullivan, W. N., Soap and Sanit, Chemicals vol. 14, No. 6, glass box, 0.3 ml. of the above-mentioned oil preparation P-l19, 1938) each 5 ml. of the above-mentioned oil prepwas uniformly atomized in the space of the box and knock aration and solutions diluted with a refined kerosene 2 0 down number of house flies was observed relative to times and 4 times were sprayed within 10 seconds. After elapsed time. The result is shown as follows:

30 Sec. 1 min. 2 min. 4 min. 8 min. 11 min.

20sec.

The present 0.5% oil preparation 2.6 7.8 36.5 59.9 80.5 87.4 Allethrin 0.3% oil preparation.. 1. 7 11. l 23. 6 58. 9 77. 7 86. 7 20 seconds the shutter was opened and house flies (adult, EXAMPLE 23 one group of about 100 flies) were exposed to the sprayed mist for 10 minutes. Then the house flies were transferred to an observation cage and the knock down number was counted. After 24 hours, kill number was also observed.

Two parts of N-(chrysanthemoxymethyl)-a,a-dimethylsuccinimide was dissolved in 20 parts .of acetone, 98 parts of 200 mesh talc powder were added thereto. After sufiiciently stirred and mixed with a mortar, and the ace- The result 15 shown as follows: tone was evaporated from the mixture to leave 1.5% dust Concentration of the Knock down ratio Mortality after 24 preparation.

zg fgg g ggg g hows (patent) House flies (adult, a group of about 50 flies) were liberated in a high Petri dish, closed with a metal wire-net F5 1% gag lid and introduced into the bottom of a settling tower. One

0:5 100 23I9 7 gram of the above-mentioned dust was scattered upward at a pressure of 20 lbs./in. The shutter was opened after EXAMPLE 20 10 seconds and the house flieswere exposed to the de- Ten parts of N-(chrysanthemoxymethyl)-u-methylsucscending dust for 10 minutes. After taken out, the house cinimide, 80 parts of xylene and 10 parts of Sorpol SM- flies were placed in a room kept at 27 C. Mortality after 200 (trade name of a surfactant of Toho Chemical Co., 20 hours amounted to 91.5 percent.

1 1 EXAMPLE 24 One part of N-(chrysanthemoxymethyl)-ot-methyl-fiethylsuccinimide was dissolved in parts of xylene and diluted with refined kerosene to make the volume 100 mls., whereby one percent oil preparation was obtained.

House flies (adult, 2. group of about 50 flies) were liberated in a high Petri dish, closed with a metal wirenet lid and introduced into the bottom of a settling tower. Ten mls. of the above-mentioned oil preparation was sprayed upward at a pressure of 20 lbs/in. The shutter was opened afterZO seconds and the house flies were exposed to the descending mist for minutes. After taken out, the house flies were placed in a room kept at 27 C. Mortality after hours amounted to 95.9 percent.

Example In similar way as in Example 19, a 100 mls. refined kerosene solution containing 2 parts of N-(chrysanthemoxymethyl)-itaconimide and 10 parts of xylene was prepared and tested.

'y-phenylitaconi-mide was prepared and tested. Mortality was 94.5% after 20 hours.

Knock down ratio of northern house mosquitoes relative to the elapse of time (percent) 3 min. 6 min. 12 min. 24 min. 48 min.

The present 1.5% mosquito coil 0 LL 0 33. 7 66. 9 86. 5

Example 32 In similar way as in Example 32, a 100 mls. refined kerosene solution containing 0.5 part of N-(chrysanthernoxymethyl) a ethyl-'y--y-dimethylitaconimide was prepared and tested against northern house mosquitoes. The

20 result was as follows:

Knock down percentage of northern house mosquitoes,

r ative to elapse of time (percent) sec. 1 min. 2 min. 4 min. 8 min. 11 min.

20 sec.

Th Qomposition oi the present Invention 2. 1 18. O 39. 1 56. 3 71. 8 82. 7

The result is shown as follows:

Concentration of the Knock down ratio Mortality after 24 active ingredient after 10 minutes hours (percent) (percent) (percent) Example 26 In similar way as in Example 20, an emulsifia-ble concentrate containing 10 parts of N-(chrysanthemoxymethyl)-'y-methylitaconimide, 10 parts of Sorpol SM-ZOO and parts of xylene was prepared and tested by using 10 mls. of the solution obtained by diluting the above-mentioned emulsifiable concentrate 10 times with water. The mortality was 87.0 percent after 20 hours.

Example 27 In similar way as in Example 22, mls. refined kerosene solution containing 0.3 part of N-(chrysanthemoxymethyl)-'yw-dimethylitaconimide and 1 part of xylene was prepared and tested.

The result is shown as follows:

What We claim is: 1. A cyclopropanecarboxylic acid ester having the for- 5 wherein R and R each is hydrogen or methyl, R and R is each hydrogen, methyl or phenyl, and R is hydrogen, methyl or ethyl.

2. An ester according to claim 1, wherein G is Knock down ratio of house flies, relative to lapse of time (percent 30 sec. 1 min. 2 min. 4 min. 8 min. 11 min.

20 sec.

The present 0.3% oil preparation 9. 8 40. 0 60. 9 80. 2 87. 3 Allethrin 0.3% oil preparation 1.6 10. 6 21. 0 51. 6 83. 9

Example 28 In similar way as in Example 23, 3 percent by weight dust preparation containing N-(chrysanthemoxymethyl)- 'y-methyl-y-phenylitaconirnide was prepared and tested. Mortality was 98.5 percent after 20 hours.

Example 29 In similar way as in Example 24, a 100 mls. refined kerosene solution containing 2 parts of N-(chrysanthemoxymethyl) 'y-y diphenylitaconimide and 10 parts of xylene was prepared and tested. Mortality was 97.8% after 20 hours.

Example 30 In similar way as in Example 23, 3 percent by weight dust preparation containing N-(chrysanthemoxymethyl)- 3. An ester according to claim 1, where G is 4. An ester according to claim 2, wherein R is hydrogen, R is hydrogen, and R is hydrogen.

5. An ester according to claim 2, wherein R is hydrogen, R is hydrogen, and R is methyl.

6. An ester according to claim 2, wherein R is hydrogen, R is hydrogen, and R is ethyl.

7. An ester according to claim 2, wherein R is methyl, R is hydrogen, and R is methyl.

8. An ester according to claim 2, wherein R is methyl, R is methyl, and R is hydrogen.

13 14 9. An ester according to claim 2, wherein R is methyl, 16. An ester according to claim 3, wherein R is methyl, R is hydrogen, and R is ethyl. R is methyl, and R is methyl.

10. An ester according to claim 3, wherein R is hydro- An ester according t l im 3, wherein R is methyl, gen, R is hydrogen, and R is hydrogen. R4 is methyl, and R5 is y 11. An ester according to claim 3, wherein R is hydro- 5 gen, R is methyl, and R is hydrogen.

12. An ester according to claim 3, wherein R is methyl,

References Cited UNITED STATES PATENTS R4 is methyl, and R5 is hydrogen 1,915,334 6/1933 SalZbCTg et al 260-243 13. An ester according to claim 3, wherein R is phenyl, 210751359 3/ 1937 salzbel'g et a1 2 R is .phenyl, and R is hydrogen. 0 3,318,766 1 7 Ka O et al. 16733 I 0 f g' xsgg zf ff g g j ifig Wherem R Phenyl, NICHOLAS s. RIZZO, Primary Examiner.

15. An ester according to claim 3, wherein R is phenyl, ALEX MAZEL Examine R is methyl, and R is hydrogen. 15 JOSE TO-VAR, Assistant Examiner. 

